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. 2022 Sep 27;8:97. doi: 10.1038/s41421-022-00468-1

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a Sample collection times during the recent COVID-2019 outbreak in Shanghai. Total COVID-19 cases are shown in solid lines (red: asymptomatic cases; green: symptomatic cases). Sequenced cases are shown in dashed line. The timeline of the first imported case report and the start of public health interventions are indicated. b Phylogenetic analysis of SARS-CoV-2 variants. SARS-CoV-2 reference genomes are shown in gray; 253 SARS-CoV-2 genomes in Shanghai are shown in red. Main SARS-CoV-2 subvariants are indicated. c Phylogenetic analysis of SARS-CoV-2 genomes grouped under the BA.2.2 subvariant. Each color indicates the region where each genome was reported from. d Phylogenetic tree under the BA.2.2 subvariant as in c. The yellow color indicates genomes carrying BA.2.2.1-characteristic mutation: A28119G (ORF8:I76V). e Mutation profiles of selected SARS-CoV-2 VOCs. Affected amino acid residues are shown below. Color gradient indicates relative mutation frequencies. Non-mutated sites are colored in gray. f The percentages and case numbers of various VOCs of SARS-CoV-2 with the A28119G (ORF8:I76V) mutation. g The percentage of BA.2.2.1-infected cases increased over time during the COVID-19 outbreak in Shanghai. h I76V at the noncovalent dimerization interface observed in the crystal structure of ORF8 (Protein Data Bank accession code: 7JTL) involving ₇₃YIDI₇₆. ORF8 models are shown as cartoon, and colored in cyan (chain A) and pink (chain B). Electron density (2F_O − F_C map, contoured at 1.5σ) is illustrated as gray mesh. van de Waals interactions involving a side-chain carbon (CD1) of I76 are indicated as dashed lines (left panel). A simple I76V mutation is introduced and V76 is refined in real space (right panel).